Todd Kolb, MD, PhD

Division of Pulmonary and Critical Care MedicineJohns Hopkins University School of MedicineTitle: "Regulation of Right Ventricular Angiogenesis in Hypoxic Pulmonary Hypertension by MIF"Term: January 15, 2013 through January 14, 2014

Summary of Research Project:

Remodeling and growth (hypertrophy) of the right ventricle (RV) allows the heart to adapt to the increased workload imposed upon it by pulmonary hypertension. In some animal models of PH, growth of new blood vessels (angiogenesis) is an important component of RV remodeling, though its regulation has not been studied. Our preliminary work shows that a small protein (MIF: macrophage migration inhibitory factor) produced by heart cells may be an important regulator of RV angiogenesis during PH. MIF appears to prevent the formation of a natural inhibitor of angiogenesis called endostatin. We are currently investigating the links between MIF, endostatin, and RV angiogenesis in mice who develop PH after chronic exposure to low oxygen levels (hypoxia). We anticipate that MIF deficiency will lead to diminished RV angiogenesis, and therefore, impaired RV adaptation to PH in this model.

Results from the these studies will significantly enhance our understanding of the regulation of RV angiogenesis and the heart’s adaptive capacity in PH. Adaptive RV remodeling helps to maintain RV function in PAH, thereby delaying symptom onset and potentially prolonging survival. By clarifying the relationship between MIF, endostatin, and RV angiogenesis, these studies may ultimately identify new biomarkers that can assist in the diagnosis of PH and evaluation of disease progression and response to treatment. Furthermore, identification of unique molecular regulators of RV angiogenesis may yield potential targets for future therapies designed to improve RV remodeling and function in PH.

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